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 Blood, 1 March 2008, Vol. 111, No. 5, pp. 2615-2620.
Prepublished online as a Blood First Edition Paper on November 29, 2007; DOI 10.1182/blood-2007-03-079855.

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HEMATOPOIESIS AND STEM CELLS

Notch target Hes5 ensures appropriate Notch induced T- versus B-cell choices in the thymus

Barbara Varnum-Finney1, Mari H. Dallas1,2, Keizo Kato1, and Irwin D. Bernstein1,2

1 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; and 2 Department of Pediatrics, University of Washington, Seattle

Notch signaling establishes boundaries in the thymus by inducing T-cell commitment and inhibiting a B-cell choice. Here, we show a significant 1.6-fold increased generation of B-cell precursors in thymuses from mice deficient for Notch target Hes5 compared with wild-type littermates. We further show that culture of bone marrow–derived progenitors with increasing densities of purified immobilized Notch ligand (Delta1ext-IgG) induced increased expression of Notch targets Hes1 and Hes5, and that although Hes5-deficient progenitors responded appropriately to high densities of ligand, they misread intermediate and low densities. Together, our results suggest that to ensure an appropriate outcome in the thymus in response to a lower threshold of induced Notch signaling, induction of the additional target Hes5 is required.


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